Intravenous mesenchymal stem cell-derived exosomes ameliorate myocardial inflammation in the dilated cardiomyopathy.

Abstract

Mesenchymal stem cells (MSCs) have been shown to be efficacy to attenuating cardiovascular inflammation; however, there are many limitations to stem cell treatment. Present study was to prove MSC-derived exosomes (MSC-Exos) could alleviating inflammatory cardiomyopathy by improving the inflammatory microenvironment of myocardium, especially by regulating the activity of macrophages. Mice were intraperitoneal injected of doxorubicin (DOX) to establish a dilated cardiomyopathy (DCM) model, and then received intravenous injection of either MSC-Exos or PBS as control. Mice receiving MSC-Exos showed improved cardiac function via echocardiography and attenuated cardiac dilation via HE staining, as well as reduced cardiomyocytes apoptosis. Expression levels of inflammatory factors were reduced. And there was a significant decrease of the inflammatory cells infiltration in the MSC-Exos treatment group comparing to the PBS group. Meanwhile, MSC-Exos could remarkably attenuate the pro-inflammatory macrophages amount in both blood and heart, which was proved that MSC-Exos relied on the JAK2-STAT6 pathway mediating macrophages activation. MSC-Exos improved the inflammatory microenvironment of dilated cardiomyopathy by regulating the polarization of the macrophage, which may hold promise for dilated cardiomyopathy clinical therapy.

• Authors: Xuan Sun, Anqi Shan, Zilun Wei, Biao Xu
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 503 Issue 4 Pg. 2611-2618 (09 18 2018) ISSN: 1090-2104 [Electronic] United States
• PMID: 30126637 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• STAT6 Transcription Factor
• Stat6 protein, mouse
• Doxorubicin
• Jak2 protein, mouse
• Janus Kinase 2

Topics

• Animals
• Apoptosis
• Cardiomyopathy, Dilated (chemically induced, diagnostic imaging, genetics, pathology)
• Doxorubicin (administration & dosage)
• Echocardiography
• Exosomes (physiology, transplantation)
• Gene Expression Regulation
• Heart Function Tests
• Inflammation
• Injections, Intravenous
• Janus Kinase 2 (genetics, metabolism)
• Macrophage Activation
• Macrophages (metabolism, pathology)
• Male
• Mesenchymal Stem Cells (chemistry, cytology)
• Mice
• Myocardium (metabolism, pathology)
• Myocytes, Cardiac (metabolism, pathology)
• Primary Cell Culture
• STAT6 Transcription Factor (genetics, metabolism)
• Signal Transduction